Provided herein are amino phosphonates and amino bis-phosphonates. Also provided are methods for the preparation and use of such compounds and their structural analogs. The present invention relates to amino phosphonates of general formula 1-3 and amino bis-phosphonates of general formula 4.

Amino phosphonates of general formula 1 have long been used as surrogates for amino acids in a variety of enzyme inhibitors and have been used in a number of applications in the pharmaceutical and agrochemical industries. Amino phosphonates of general formula 2 or 3, have been used extensively as inhibitors of proteases and other enzymes ((a) Mader, M. M.; Bartlett, P. A. Chem. Rev. 1997, 97, 1281. (b) Powers, J. C.; Asgian, J. L.; Ekici, O. D.; James, K. E. Chem. Rev. 2002, 102, 4639. (c) De Lombaert, S. et al. Bioorg. Med. Chem. Lett. 1995, 5, 151. (d) De Lombaert, S. et al. J. Med. Chem. 2000, 43, 488. (e) Bird, J. et al. Bioorg. Med. Chem. Lett. 1995, 5, 2593. (f) Ding, J.; Fraser, M. E.: Bartlett, P. A: Am. Chem. Soc., 1998, 120, 4610) and have exhibited a range of useful activities as pharmaceuticals and agrochemicals (Quin, L. D. A Guide to Organophosphorus Chemistry; Wiley-Interscience: New York, 2000) For example, amino phosphonates have served as key structural components of antiviral agents, antitrypanosomal agents, antibacterial agents and anticancer agents. Amino phosphonates have also been used as agrochemicals and as chelating agents or surfactants in industrial applications
Amino bis-phosphonates of general formula 4 have been used as diphosphate mimics for the treatment of bone resorption diseases, and as antiparasitic agents ((a) Szabo, C. M. etal J. Med. Chem. 2002, 45, 2185. (b) Morty, R. E. etal. Biochemical Pharmacology, 2000, 60, 1497. (c) Rodan, G. A.: Martin, T. J. Science 2000, 289, 1508).
The present invention also provides a process for the synthesis of functionalized amino phosphonates and amino bis-phosphonates via the one-step three-component reaction among an amine derivative, a carbonyl derivative and an organoboron compound. This process is related to the previously reported general method for the synthesis of amine derivatives, including amino acids and amino alcohols. ((a) Petasis, N. A.; Zavialov, I. A., 2001, U.S. Pat. No. 6,232,467. (b) Petasis, N. A. 2003, U.S. Pat. No. 6,602,817 B1. (c) Petasis, N. A.; Zavialov, I. A., J. Am. Chem. Soc., 1997, 119, 445. (d) Petasis, N. A.; Goodman, A.; Zavialov, I. A. Tetrahedron, 1997, 53, 16463. (e) Petasis, N. A.; Zavialov, I. A., J. Am. Chem. Soc., 1998, 120, 11798. (f) Prakash G. K. S.; Mandal M.; Schweizer, S.; Petasis, N. A.; Olah, G. A. J. Org. Chem., 2002, 67, 3718. (g) Petasis, N. A.; Patel, Z. D., Tet. Lett, 2000, 41, 9607).